High-resolution NMR spectroscopy of subnanoliter liquid samples
EMSL Project ID
48056
Abstract
Nuclear magnetic resonance (NMR) spectroscopy is recognized as an important and often indispensible analytic tool for structure elucidation, molecular identification, measurements of dynamics (on timescales from nanoseconds to hours), and imaging. With applications in medicine, biology, materials science, and chemistry, NMR techniques continue to evolve and contribute to the solutions of important scientific and industrial problems. A longstanding limitation of NMR spectroscopy, however, is the need for samples with macroscopic dimensions. While detection of nuclear magnetic resonance in microscopic samples has been demonstrated, commercial attempts to miniaturize instrumentation for high-resolution NMR spectroscopy have so far yielded detectors with characteristic dimensions of ~ 1 mm or larger, which in general perform poorly for microscopic samples.The inability to perform NMR spectroscopy for microscopic samples is a significant technical gap. As lab-on-a-chip technology assumes a more prominent role in a range of fields, the capability to integrate high-resolution NMR with microfluidic chips will become increasingly desirable. On a practical level, cost, waste, and risks to safety are typically minimized when microfluidic chips replace conventional tools for preparing and analyzing samples. On a fundamental level, the emerging capability to study individual microsystems such as biological cells or aerosol particles using a range of tools will yield understanding of microscopic heterogeneity and interaction dynamics. Such understanding is essential for effective treatment of disease and in vitro cell culturing in biotechnology, for example. The development of high-resolution NMR as a tool for studying microfluidic samples, including individual cells with micrometer dimensions, would be a notable scientific advance.
Recent progress in the design of scalable NMR detectors, together with insights into the spin physics of efficient small-volume detection, have created an opportunity to achieve this goal. A microstrip waveguide formed on a printed circuit board using standard microfabrication methods can function as a sensitive NMR detector, easily scalable for the study of samples with characteristic dimensions of a few micrometers. Such waveguides have been used for the most sensitive acquisition of conventional high-resolution spectra performed so far. A practical advantage of the design is one-sided detection: the waveguide can simply be placed under the sample, which allows for easy integration of the NMR detector into microfabricated systems.
We are developing microstrip waveguide detectors for NMR spectroscopy of liquid samples with micrometer dimensions. The use of such detectors for spectroscopy has so far been limited to only two studies, most likely because of the limited spectral resolution achieved in these studies. However, pulse sequences that can eliminate the spectral broadening observed in these experiments have been known for decades. In combination with the use of spin echoes during signal acquisition, such pulse sequences are optimal both for spectral resolution and for detection sensitivity. By using microstrip waveguide detectors together with pulse sequences designed for small-volume samples, we aim to show that NMR spectra of subnanoliter samples can be measured with spectral resolution comparable to that of commercial detectors, which typically require samples of volume ~ 200 microliters.
Project Details
Start Date
2013-05-28
End Date
2013-09-30
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members